There is considerable evidence to suggest that some foam cells observed in atherosclerotic lesions are derived from macrophages. The mechanism(s) leading to cholesteryl ester accumulation in these cells is unknown. In this proposal, the in vitro preparation of complexes containing LDL, heparin, denatured collagen, and fibronectin are described. Preliminary studies indicate that macrophages endocytose 10X more complex-derived LDL than native LDL. The endocytosed complexderived LDL remained largely undegraded and led to cholesteryl ester accumulation in these cells. Experiments proposed here are designed to: 1) Further characterize LDL-glycosaminoglycan-fibronectin-collagen complexes and their interaction with macrophages, 2) Explore mechanisms of enhanced endocytosis and impaired degradation, and 3) Investigate the interaction of complexes with monocytes, stimulated macrophages and smooth muscle cells. Results of these experiments should provide valuable information concerning the uptake and degradation by macrophage of LDL complexed to components of the vascular extracellular matrix. These findings may provide further insight into foam cell development during atherogenesis.
| Falcone, D J; Salisbury, B G (1988) Fibronectin stimulates macrophage uptake of low density lipoprotein-heparin-collagen complexes. Arteriosclerosis 8:263-73 |
| Falcone, D J (1986) Fluorescent opsonization assay: binding of plasma fibronectin to fibrin-derivatized fluorescent particles does not enhance their uptake by macrophages. J Leukoc Biol 39:1-12 |
| Salisbury, B G; Falcone, D J; Minick, C R (1985) Insoluble low-density lipoprotein-proteoglycan complexes enhance cholesteryl ester accumulation in macrophages. Am J Pathol 120:6-11 |
